Recurrence of focal segmental glomerular sclerosis (FSGS) in the allograft following renal transplantation can be graft threatening. To assess risk factors associated with FSGS recurrence, we analyzed 22 patients with FSGS who underwent transplantation between 1996 and 2004. Five patients (Group I, 23%) developed FSGS post-transplantation. Of these patients, 60% had undergone bilateral nephrectomy (BN) for progressive disease compared with none of the patients that were free of recurrence (Group II) (p = 0.0006). Other factors linked with recurrent FSGS were time to first dialysis (Group I: 3.1 +/- 1.1 yr vs. Group II: 11.9 +/- 1.9 yr; p = 0.03), pre-transplant proteinuria (Group I: 7.0 +/- 1.8 g/d vs. Group II: 2.5 +/- 0.7 g/d; p = 0.02), young age at transplantation (p = 0.09) and female sex (Group I: 80% vs. Group II: 24%; p = 0.021). Eighty percent of Group I patients received a living related transplant vs. 24% in Group II (p = 0.021). All grafts continue to function at last follow-up with comparable serum creatinines. Overall, post-transplant FSGS recurrence may be associated with BN, severity of pre-transplant FSGS, female gender, and living donation. These patients should be monitored closely for early recurrence and may benefit from early plasmapheresis to restore and facilitate long-term graft function.